Ammonium Chloride → 2-(Pyridin-4-yl)-2-(6-(trifluoromethyl)pyridin-3-yl)acetonitrile

HRID 512176

Reaction equation

HRID 512176 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[N:8]=[CH:7][C:6]([CH2:9][C:10]#[N:11])=[CH:5][CH:4]=1.CC([O-])(C)C.[K+].Cl.Br[C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1.[NH4+].[Cl-]>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[N:25]1[CH:26]=[CH:27][C:22]([CH:9]([C:6]2[CH:7]=[N:8][C:3]([C:2]([F:12])([F:1])[F:13])=[CH:4][CH:5]=2)[C:10]#[N:11])=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 881004-Bromopyridinium chlorideHCID 23665647Potassium tert-butoxideHCID 508511273-Pyridineacetonitrile, 6-(trifluoromethyl)-

Product 1

HCID 867162032-(Pyridin-4-yl)-2-(6-(trifluoromethyl)pyridin-3-yl)acetonitrileYield 25.7%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
60 °C

Procedure

A dried flask was charged with 2-(6-(trifluoromethyl)pyridin-3-yl)acetonitrile (1.0 g, 5.38 mmol) in DME (20 ml). The mixture was degassed and filled with N2, then t-BuOK (30 ml, 30 mmol, 1M in THF), 4-bromopyridine hydrochloride (2.1 g, 10.7 mmol) and Pd(dppf)Cl2 (39.6 mg, 0.538 mmol) was added. The mixture was stirred at 60° C. for 3 h. After cooling to room temperature, sat.aq NH4Cl (15 ml) was added and the solution was extracted with EtOAc (3×30 ml). The combined organic layers were washed with brine and dried over Na2SO4, concentrated in vacuo. The residue was purified by column chromatography on silica gel (EtOAc: Petroleum ether=4:1) to give 2-(pyridin-4-yl)-2-(6-(trifluoromethyl)pyridin-3-yl)acetonitrile (360 mg, yield: 25.7%). 11-1 NMR (CDCl3 400 MHz): δ8.75 (d, J=1.6; Hz, 1H), 8.71 (d, J=6.0; Hz, 2H), 7.90 (dd, J=8.0; Hz, 2.0; Hz, 1H), 7.77 (d, J=8.4; Hz, 1H), 7.31 (d, J=6.0; Hz, 2H), 5.26 (s, 1H).

Workup

  1. customThe mixture was degassed
  2. additionfilled with N2
  3. temperatureAfter cooling to room temperature
  4. extractionthe solution was extracted with EtOAc (3×30 ml)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography on silica gel (EtOAc: Petroleum ether=4:1)

Sources & evidence

ORD record
ord-bb42b0516d5e4c24b8b8b698727effa8
Source dataset
uspto-grants-2015_08
Patent number
US09102591B2

Linked notes

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